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35 Cards in this Set

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  • Back
What are neurodengenerative diseases characterized by?
progressive loss of neurons in the CNS
Which type of neurons is PD have a loss in?
PD is caused by a loss in dopaminergic neurons in specific regions of the brain.
What are the two anatomical regions within the basil lamina which are linked by dopaminergic neurons?
substantia nigra and the corpus stratium
What plays an impt. role in controlling motor movement?
GABAnergic output from the corpus stratium,
The GABAnergic output is regulated by which two neurotransmitters?
dopamine and acetylcholine
What gives rise to symptoms of dysfunctional motor control seen in PD?
It is the imbalance of dopamine regulation relative to ACh regulation on GABAnergic output.
When corpus stratium is stimulated by dopamine what occurs?
the dopamine receptors have a negative (decreased) effect on GABAnergic output from the corpus stratium.
What is contained within the substantia nigra?
many dopaminergic neurons that project into the corpus stratum. When stimulated, these dopaminergic neurons release dopamine to bind at dopamine receptors.
What is contained within the corpus stratium?
cholonergic neurons that synthesize and secrete ACh.
What occurs when ACh is released from the corpus stratium?
When released, the ACh stimulates cholinergic receptors, resulting in an positive (increased) effect on GABAnergic output from the corpus stratium.
In patients without neurodegenerative diseases. What occurs?
The GABAnergic output from the corpus stratium affecting motor movement is kept in balance by dopamine (neg.) and ACh (pos.)
What are the 2 general approaches to drug therapy curretnyl used in the management of PD?
1. Replace the dopaminergic effect that is lost secondary to the destruction of dopaminergic neurons in the substantia nigra and the corpus stratium, and
2. Inhibit the excess cholinergic acitivity that occurs secondary to the loss if dopaminergic activity.
What are the symptoms of PD?
limb muscle rigidity, resting tremor (tremor that goes away with movement), bradykinesia, and postural instability (impaired postural balance)
Name the 5 different groups that antiparkinsonism drugs can be divided into.
1. Dopamine precursor
2. Dopamine agonist
3. MAO-B Inhibitors
4. COMT Inhibitors
5. Anticholinergics
Name 2 drugs which are dopamine precursor.
Levodopa and Levodopa and Carbidopa
Why is Levodopa used?
Because when administered orally, it can cross the blood brain barrier to get into the CNS. ONce it is in the CNS, levodopa is converted to dopamine by the enzyme dopa decarboxylase.
Why is the administration of Levodopa and Carbidopa better then Levodopa by itself?
Because most of the dose of Levodopa is converted to dopamine before it crosses in the blood brain barrier. Therefore, Carbidopa is used with Levodopa because it is an inhibitor of dopa decarboxylase only outside of the CNS.
Name the 5 dopamine agonists.
Amantadine, Apomorphine, Bromocriptine, Pramipexole, and Ropinirole
Which 2 dopamine agonist are agonist are D2 receptors, and also interact with D1 receptors.
Bromocriptine and Apomorphine. Interaction with D1 receptors outside of the CNS worsen the adverse effects of Bromocriptine.
Which drug is a dopamine agonist and a antiviral agent useful for the prevention of influenza A virus infection.
Amantadine
Which 2 dopamine agonist are selective D2 agonists?
Ropinirole and pramipexole. Selective D2 agonists avoid adverse effects common to less selective dopamine agonists.
What is only current selective MAO-B inhibitor marketed for management of PD?
Selegiline
TRUE/FALSE. Dopamine is a catecholamine neurotrasmitter, and like other catecholamine neurotransmitters, it is inactivated by metabolism.
TRUE
What is one of two major enzymes that inactivates catecholamines by enzymatic metabolism?
Monoamine oxidase (MAO)
Name the two forms of MAO's and there difference.
MAO-A: found mostly outside of the CNS
MAO-B: found mostly in the CNS
Which enzyme contributes significantly to the inactivation of both levodopa and dopamine?
catechol-O-methyl transferase (COMT)
When do patients use COMT inhibitors?
They are indicated for use with levodopa when patients show signs of levodopa therapy "wearing off"
Name 1 COMT inhibitor.
Entacapone
Name 1 antimuscarinic drug used in PD therapy?
Benztropine
The loss of dopaminergic activity results in an indirect _______ in cholinergic activity.
increase. So antimuscarinics drugs with CNS activity block central cholinergic receptors
What are the symptoms of PD that are reduced?
1. Bradykinesia (poverty mov't)
2. Muscle rigidity
3. Resting tremor (a fine tremor that goes aaway upon movement)
4. Postural instability (impaired postural balance
What is a common adverse effect of levodopa therapy?
nausea, cardiovascular toxicity--cardiac arryhthmia and atrial fibrillation (reduced when levodopa and carvidopa are administered together. When given alone Levodopa causes substantial anorexia, nausea, vomiting. Also, dyskinesia, adverse mental effects (hallucinations, nightmares, depression, anxiety, agitation, insomnia, and the fluctuations ("wearing off")
What are the adverse effects of dopamine agonist?
significant GI adverse effects and adverse mental effects (hallucinations, depression, nightmares, anxiety, agitation, insomnia)
What are the adverse effects of dopamine agonist that are not selective for D2 receptors?
postural hypotension secondary to activation of peripheral D1 receptors
What are the antimuscarinic adverse effects?
dry mouth, sedation, urinary retention, and constipation